Diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, which was available as a potent aryl-acetic acid drug in 1974. Diclofenac sodium is used clinically for relieving fever or pain. It is widely used for treating chronic rheumatoid arthritis, spinal deformity, neuralgia, flu-like syndrome, lupus erythematosus, and postoperative pain and inflammation, etc. Diclofenac sodium has been favored by doctors and patients because of its good efficacy, fast absorption by oral administration, fast action and excretion, little side effects during long-term use, and small differences between individuals. The chemical structural formula of diclofenac sodium is shown as (1):

GB Patent No. 1132128 and U.S. Pat. No. 3,558,690 disclose a method for producing diclofenac sodium (1), where o-(bromo)benzoic acid was used as a the starting material to prepare the key intermediate 2,6-dichlorodiphenylamine by Ullmann condensation and decarboxylation. 2,6-Dichlorodiphenylamine was then subjected to acylation, cyclization and ring-opening hydrolysis/salification to obtain diclofenac sodium (1). This method was the earliest synthetic route for the industrial production of diclofenac sodium in China, which involved the commercially available raw materials. However, such process was longtime consuming with the low total yield and the serious environmental pollution. NL Patent No. 6604752 and JP Patent No. 23418 disclosed a method of synthesizing 2,6-dichlorodiphenylamine with bromobenzene and 2,6-dichloroaniline by Ullmann condensation with a yield of nearly 50%. This method has been widely used in the past, but its industrial application was very limited because a small amount of by-products such as N-phenyl-2-chloro-6-bromoaniline produced during synthesis was difficult to separate. Besides, the traces of aromatic bromide may cause the side effects such as stomach ulcers. EP Patent No. 0380712 and WO Patent No. 022522 discloses a method of producing diclofenac sodium (1) in three steps in a one-pot including acylation, etherification and Chapman rearrangement, where aniline was used as a starting material. Fen'er Chen et al. (Chinese Journal of Pharmaceuticals, 1998, 29, 339) make improvements to such method, but leading to the serious pollution caused by wastes, high labor safety requirements and greatly increased costs. Fen′er Chen et al. (Chinese Patent Publication No. CN 1580039A) discloses a method for synthesizing diclofenac sodium (1) using cyclohexanone as a starting material though a series of chlorination, carboxylation, hydrogenation, condensation, and aromatization/salification. Although this method involved a high yield, its industrial application was limited due to the long process and highly toxic organophosphorus reagent. U.S. Pat. No. 4,978,773 and Bingchang Qin et al. (Applied Chemical Industry, 2008, 3, 275) disclose a method of producing diclofenac sodium in which 2,6-dichlorodiphenylamine and chloroacetyl chloride are used as primary raw materials, followed by acylation, intramolecular Friedel-Craft alkylation and alkaline hydrolysis ring-opening reaction. But in this method, the reaction process was longtime consuming with the relatively low overall yield.
Therefore, there is an urgent need to develop a method for synthesizing diclofenac sodium with the high yield and low cost to overcome the defects in the above methods.